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Jack Lee
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MS 01 - Clinical Development of Novel Agents (ID 523)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:S. Mandrekar, M. Mori
- Coordinates: 10/16/2017, 11:00 - 12:30, Main Hall
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MS 01.02 - Are We Categorizing Biomarkers Too Quickly? (ID 7641)
11:20 - 11:40 | Presenting Author(s): Jack Lee
- Abstract
- Presentation
Abstract not provided
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OA 07 - Biomarker for Lung Cancer (ID 659)
- Event: WCLC 2017
- Type: Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:Philip Christopher Mack, Shinichi Toyooka
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 503
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OA 07.02 - Characteristics of Lung Cancer Cell-Free Tumor DNA (CfDNA) Shedding and Correlation with Tumor Burden as Measured by RECIST (ID 9663)
15:55 - 16:05 | Author(s): Jack Lee
- Abstract
- Presentation
Background:
cfDNA is a promising biomarker for early recurrence detection and disease monitoring in the NSCLC curative setting. However, less is known about cfDNA shedding characteristics and correlation with tumor burden in advanced NSCLC.
Method:
We reviewed cfDNA results of NSCLC patients tested at our institution between November 2015 and December 2016 with Guardant 360, a comprehensive cfDNA assay that detects genomic alterations in 70-73 cancer genes. 141 cases with evaluable imaging were selected for this analysis, enriching for EGFR and KRAS mutated cases to facilitate comparisons of major genomic subtypes (Table 1). Tumor burden was approximated using the sum of longest diameters (SLD), per RECIST v1.1.
Result:
There was a statistically significant correlation of moderate strength between cfDNA maximum variant allele frequency (VAF) detected and SLD (Spearman’s rho = 0.35, p < 0.001). This correlation was strongest in KRAS mutant cases (rho = 0.52, p = 0.001) and weakest in EGFR mutated tumors (rho = 0.21, p < 0.24). Multi-variate regression that included stage, histology, and mutation status confirmed the predictive value of cfDNA VAF for SLD (p = 0.03). TP53 mutants had higher cfDNA VAF (Wilcox p < 0.001), even after accounting for SLD. Increased cfDNA VAF was also seen with EGFR mutants and patients with visceral metastasis, though possibly confounded by concomitant EGFR amplification and increased tumor burden, respectively. CNS metastasis was not associated with differential cfDNA shedding. Figure 1
Conclusion:
In this primarily metastatic cohort, cfDNA VAF correlated with radiographic assessment of tumor burden by RECIST. This correlation was partially mediated by the presence of key driver mutations. TP53 and EGFR mutant tumors and the presence of visceral metastasis are associated with higher cfDNA VAF. These findings have potential implications for the use of cfDNA in advanced-stage NSCLC disease monitoring, where RECIST is more clinically applicable than formal volumetrics.
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OA 13 - Immuno-Biology (ID 677)
- Event: WCLC 2017
- Type: Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Hiroyuki Suzuki, Scott N. Gettinger
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 301 + 302
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OA 13.05 - Immune, Molecular and T Cell Repertoire Landscape of 235 Resected Non-Small Cell Lung Cancers and Paired Normal Lung Tissues (ID 8766)
11:45 - 11:55 | Author(s): Jack Lee
- Abstract
- Presentation
Background:
Non-small cell lung cancer (NSCLC) is characterized by a high mutational load. Accordingly, it is also among the tumor types responding to immune checkpoint blockade, likely through harnessing of the anti-tumor T cell response. However, the lung is continuously exposed to the outside environment, which may result in a continuous state of inflammation against outside pathogens unrelated to the tumor microenvironment. Therefore, further investigation into the T cell repertoire and T cell phenotypes across normal lung and tumor is warranted.
Method:
We performed T cell receptor (TCR) sequencing on peripheral blood mononuclear cells (PBMC), normal lung, and tumor from 225 NSCLC patients, among which, 96 patients were also subjected to whole exome sequencing (WES) of PBMC, tumor and normal lung tissues. We further performed Cytometry by Time-of-Flight (CyTOF) on 10 NSCLC tumors and paired normal lung tissues to phenotype immune and T cell subsets.
Result:
Comparison of the T cell repertoire showed 9% (from 4% to 15%) of T cell clones were shared between normal lung and paired tumor. Furthermore, among the top 100 clones identified in the tumor, on average 57 (from 0 to 95) were shared with paired normal lung tissue. Interestingly, T cell clonality was higher in the normal lung in 89% of patients suggesting potential differences in the immune response and immunogenicity. A substantial number of somatic mutations were also identified not only in NSCLC tumors (average 566; from 147 to 2819), but also in morphologically normal lung tissues (average 156; from 50 to 2481). CyTOF demonstrated striking differences in the immune infiltrate between normal lung and tumor, namely a lower frequency of PD-1+CD28+ T cells (both CD4+ and CD8+) in the normal lung (2.7% versus 3.0% in tumor). In addition, a unique GITR+ T cell subset (0.96%) was entirely restricted to the normal lung. Conversely, increases in regulatory T cell frequency (CD4+FoxP3+) were observed in the tumor (10.4% vs 1.7% in normal lung), further highlighting the differences in T cell phenotype and response across normal lung and tumor.
Conclusion:
These results suggest that a substantial proportion of infiltrating T cells in NSCLC tumors may be residential T cells associated with response to environmental factors. However, normal lung and NSCLC tumors carry T cells of distinct phenotypes including increases in immunosuppressive T cells within the tumor which may further highlight the differences in the anti-tumor immune response.
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P2.04 - Clinical Design, Statistics and Clinical Trials (ID 705)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.04-014 - Computing the Impact of Immunotherapy on NSCLC Landscape: The Advanced Non-Small Cell Lung Cancer Holistic Registry (ANCHoR) (ID 9505)
09:30 - 09:30 | Author(s): Jack Lee
- Abstract
Background:
Anti-PD-1 and anti-PD-L1 antibodies including pembrolizumab, nivolumab and atezolizumab have entered clinical practice in the management of metastatic NSCLC as monotherapy and immunotherapy-based combinations. We have established a real-world Advanced Non-Small Cell Lung Cancer Holistic Registry (ANCHoR) to understand how the emergence of immunotherapy impacts choice of treatment, clinical outcomes, and patient reported outcomes (PROs) in the different histo-molecular subtypes of metastatic NSCLC. The objectives of ANCHoR are to determine the treatment choice and treatment sequence by PD-L1 status in the various histo-molecular categories of NSCLC and to understand the impact of such treatment choice on response rates, progression-free survival (PFS), and overall survival (OS). Additionally we will measure the impact the treatment choices have on the PROs by utilizing the validated instruments, EuroQol-5D version 5L (EQ-5D-5L) and MD Anderson Symptom Inventory module specific to lung cancer (MDASI-LC).
Method:
The study will enroll patients with metastatic NSCLC diagnoses who are treated at MD Anderson Cancer Center (MDA) between January 1, 2017 and December 31, 2020. The study period will end on June 30, 2021 to allow a minimum of six months of follow-up. Trained abstractors will collect demographic, diagnostic, clinical, molecular (biomarker and PD-L1), treatment (regimens utilized in sequence and reason for discontinuation), response and survival (including PFS and OS), health care resource utilization and PRO (EQ-5D-5L and MDASI-LC) information that will be integrated in a comprehensive database. Information from the MDA electronic medical record will be extracted and populated in the GEnomic Marker-guided therapy INItiative (GEMINI) database and the PRO database which are linked. EQ-5D-5L followed by MDASI-LC will be completed directly by the patients and these will be automatically populated in the web-based PRO database at treatment initiation, at the time of response assessments and when switching lines of therapy.
Result:
Interim analysis will be conducted every six months to measure the impact of immunotherapy over time. Study results will be presented using descriptive statistics for continuous variables (mean, standard deviation, median, and interquartile range), categorical variables (frequency and proportions), and time-to-event variables (Kaplan-Meier). Regression models will be used for estimating the relationship between dependent variable and one or more predictors. Cox proportional hazards model will be used to estimate hazard ratios for time-to-event outcomes.
Conclusion:
The ANCHoR study is the first comprehensive registry of its kind that will enable the quantification of the changing impact of immunotherapy on the real-world NSCLC treatment landscape.
